Cytogenetics Laboratory Research Articles

Investigation of the influence of calibration practices on cytogenetic laboratory performance for dose estimation

Purpose: In the frame of the QA program of RENEB, an inter-laboratory comparison (ILC) of calibration sources used in biological dosimetry was achieved to investigate the influence of calibration practices and protocols on the results of the dose estimation performance as a first step to harmonization and standardization of dosimetry and irradiation practices in the European biological dosimetry network.Materials and methods: Delivered doses by irradiation facilities used by RENEB partners were determined with EPR/alanine dosimetry system. Dosimeters were irradiated in the same conditions as blood samples. A short survey was also performed to collect the information needed for the data analysis and evaluate the diversity of practices.Results: For most of partners the deviation of delivered dose from the targeted dose remains below 10%. Deviations larger than 10% were observed for five facilities out of 21. Origins of the largest discrepancies were identified. Correction actions were evaluated as satisfactory. The re-evaluation of some ILC results for the fluorescence in situ hybridization (FISH) and premature chromosome condensation (PCC) assays has been performed leading to an improvement of the overall performances.Conclusions: This work has shown the importance of dosimetry in radiobiology studies and the needs of harmonization, standardization in irradiation and dosimetry practices and educational training for biologists using ionizing radiation.

Change in Pattern of HER2 Fluorescent in Situ Hybridization (FISH) Results in Breast Cancers Submitted for FISH Testing: Experience of a Reference Laboratory Using US Food and Drug Administration Criteria and American Society of Clinical Oncology and College of American Pathologists Guidelines.

Purpose In 1998, the US Food and Drug Administration (FDA) approved human epidermal growth factor receptor 2 (HER2) testing guidelines to determine eligibility for HER2-directed therapy (HDT) in breast cancer. ASCO and the College of American Pathologists published immunohistochemistry (IHC) and fluorescent in situ hybridization (FISH) HER2 testing guidelines in 2007 (AC2007) and updated these guidelines in 2013 (AC2013). We compared the HER2 FISH amplification frequency using these three guidelines. Methods Patient samples that were sent to the Mayo Clinic cytogenetics laboratory for FISH testing (n = 2,851; from November 2013 to October 2014) were analyzed. Frequency of HER2 FISH amplification was examined and impact of AC2013 assessed. Results IHC results were available for 1,922 patient samples (67.4%), 137 of which were from Mayo Clinic. Distribution was 2.4% IHC 0, 7.9% IHC 1+, 84.8% IHC 2+, and 2.5% IHC 3+. Among IHC 2+ patients, HER2 FISH positivity was 11.8% (FDA), 9.4% (AC2007), and 24.1% (AC2013). Overall, 11.8% (n = 339) were positive with a FISH ratio ≥ 2.0, 1.3% (n = 35) with a FISH ratio ≥ 2.0 despite a HER2 signal < 4.0, and 3.0% (n = 86) with HER2 signal ≥ 6.0 despite FISH ratio < 2.0. Among 405 patients (14.2%) who were initially considered FISH-equivocal (ratio < 2.0 with HER2 signal ≥ 4.0, but < 6.0; AC2013), use of an alternative chromosome 17 probe reassigned 212 (7.4% overall) patients to FISH-positive and 36 (1.3% overall) patients to FISH-negative, whereas 157 (5.5% overall) patients remained equivocal. Final HER2 positivity with AC2013 (23.6%) was increased (P < .001) compared with FDA (13.1%) and AC2007 (11%) guidelines. Conclusion In a reference laboratory cohort that was highly enriched for IHC 2+ patient samples, AC2013 guidelines led to a larger number of FISH-equivocal patients. Approximately one half of these FISH-equivocal patients (7.4% overall) became HER2-positive upon alternative FISH probe testing. However, these patients would not have participated in the pivotal HDT trials. Clinical utility data on HDT benefit in these patients and other special subsets are needed.

A survey of neural network based automated systems for human chromosome classification

Chromosome classification and karyotype establishment are important procedures for genetic diseases diagnosis. Various computer-aided systems have been developed to automate this tedious and time consuming task, which is performed manually in most cytogenetic laboratories. This paper provides a comprehensive review of past and recent research in the area of automatic chromosome classification systems. We start by reviewing methods for feature extraction, followed by a neural network based chromosome classifiers survey. We sum-up various techniques and methods in this area of research and discuss important issues and outcomes within each study for both chromosome feature extraction and classification. Although the ANN based chromosome classifiers are the main topic of this survey, a number of classifiers based on other algorithms are exposed to give an overall idea about additional techniques employed in chromosome classification.

Cytogenetic analysis in women with primary and scondary amenorrhea in iran: retrospective study on 110 patients

The absence of menstrual periods for one or more periods is called amenorrhea. Primary amenorrhea means the lack of its occurrence until the age of 16 years. Secondary amenorrhea refers to situations that a person has experienced menstruation periods in the past and then stops its occurrence. Amenorrhea is a symptom, not a disease that can cause due to disorders of hypothalamus and pituitary glands, disorders of sexual glands and deformities of the uterus and ovaries. Due to the clinical importance of reproductive in life and non-reproductive of women amenorrhea due to ovarian function, this study has been conducted in order to determine the prevalence and type of chromosomal abnormalities in women referred to the Cytogenetic Laboratory of Cellular and Molecular Research Center, in University of Medical Sciences of Qazvin. Karyotype analysis and its relationship with phenotype were performed on 110 Iranian female patients with primary and secondary amenorrhea. Metaphase chromosomes were prepared and analyzed by G-banding technique and were evaluated to examine the mosaicism of 100 cells of lymphocytes cells. Karyotype of 91 women (82.72%) was normal and chromosomal abnormalities in 19 patients out of 110 patients (17.37%) were observed with primary and secondary amenorrhea. Primary amenorrhea was observed in 17 of these patients, two of whom also had a secondary amenorrhea. Monosomy chromosome X (6 Cases- 31.57%) and Monosomy chromosome Y (6 Cases- 31.57%) was the most common disorders observed in the women with primary amenorrhea. Monosomy mosaic and trisomy chromosome X were observed in 2 cases of women with secondary amenorrhea (21.81% of the whole statistical sample). The overall prevalence of chromosomal abnormalities was between 15.9 % and 63.3% among patients with primary amenorrhea, that our findings in chromosomal analysis of these women (19.76%) confirm it. Keywords: cytogenetic, primary amenorrhea, secondary amenorrhea, chromosomal abnormalities

Development of a curriculum in molecular diagnostics, genomics and personalized medicine for dermatology trainees.

Results of molecular studies are redefining the diagnosis and management of a wide range of skin disorders. Dermatology training programs maintain a relative gap in relevant teaching. To develop a curriculum in molecular diagnostics, genomics and personalized medicine for dermatology trainees at our institution. The aim is to provide trainees with a specialty-appropriate, working knowledge in clinical molecular dermatology. The Departments of Dermatology and Pathology and Laboratory Medicine collaborated on the design and implementation of educational objectives and teaching modalities for the new curriculum. A multidisciplinary curriculum was developed. It comprises: (i) assigned reading from the medical literature and reference textbook; (ii) review of teaching sets; (iii) two 1 hour lectures; (iv) trainee presentations; (v) 1-week rotation in a clinical molecular pathology and cytogenetics laboratory; and (vi) assessments and feedback. Residents who participated in the curriculum to date have found the experience to be of value. Our curriculum provides a framework for other dermatology residency programs to develop their own specific approach to molecular diagnostics education. Such training will provide a foundation for lifelong learning as molecular testing evolves and becomes integral to the practice of dermatology.

Anomalías cromosómicas en abortos espontáneos

Introducción: El 15 a 20% de las gestaciones clínicas terminan en aborto espontáneo y 25% de las mujeres sufrirán un aborto a lo largo de su vida. En más del 50% de los casos de abortos espontáneos se puede identificar una o más anomalías cromosómicas. Objetivos: Determinar la frecuencia de anomalías cromosómicas en restos de abortos espontáneos y su relación con edad materna y otros parámetros como la edad gestacional. Diseño: Estudio de tipo observacional, descriptivo, transversal sobre base de datos secundaria. Institución: Laboratorio de Citogenética del Instituto de Medicina Genética. Material: Muestras de abortos espontáneos. Métodos: Se realizó el análisis de base de datos de 2 319 muestras de abortos espontáneos recibidos en el periodo de enero 1996 a diciembre 2013. Principales medidas de resultados: Frecuencia de anomalías cromosómicas. Resultados: De todos los casos analizados (2 319), 1 595 muestras presentaron cariotipo anormal (68,8%). De las anomalías numéricas (1 395/1 595), el 83,2% correspondió a aneuploidías y 16,8% a poliploidías. Los cariotipos mosaicos estuvieron presentes en 5,5% (87/1 595) y las anomalías estructurales en 3,5% (56/1 595). Se encontró dependencia entre las trisomías y la edad materna (X2 p&lt;0,05). Conclusiones: El 68,8% de los abortos estudiados presentó alguna alteración cromosómica, siendo las aneuploidías las anomalías numéricas más frecuentes, con predominio de las trisomías (58,4%), las cuales estuvieron relacionadas con el incremento de la edad materna.

Trophoblast Retrieval and Isolation From the Cervix for Noninvasive, First Trimester, Fetal Gender Determination in a Carrier of Congenital Adrenal Hyperplasia.

Congenital adrenal hyperplasia (CAH) is an autosomal recessive defect in cortisol biosynthesis that elevates fetal androgen levels to cause genital ambiguity and external genital masculinization in newborn females. Introducing dexamethasone in utero by 7 weeks gestation precludes virilization of affected females. However, identification of a male fetus prior to week 7 could avert the necessity of steroid treatment in half of pregnancies at risk of CAH. We recently introduced trophoblast retrieval and isolation from the cervix (TRIC), an approach that noninvasively isolate homogeneous trophoblast cells from pregnant women as early as 5 weeks gestation, using a Papanicolaou test. Here, we have used TRIC to correctly identify male fetal DNA when both parents were carriers of the mutation that produces CAH and previously produced an affected child. Trophoblast cells (1400) obtained by TRIC were assessed using immunocytochemistry with an antibody against the trophoblast-specific β subunit of human chorionic gonadotropin, which labeled 100% (17 of 17) of isolated cells, while none of the excluded maternal cervical cells were labeled. The isolated cells were examined by fluorescent in situ hybridization for chromosomes 18, X, and Y at a clinical cytogenetics laboratory, demonstrating 100% (18 of 18) of cells to be diploid 18/XY. Aliquots of DNA obtained from the isolated cells assayed for SRY and RNASEH genes by TaqMan assays confirmed a male fetus. This case study demonstrates the utility of TRIC to accurately identify fetal gender as a means of reducing the need for prophylactic administration of exogenous steroids in pregnancies at risk of CAH.

23 - Utility of Genome-Wide Characterization of B-Cell Acute Lymphoblastic Leukemia Using SNP-Based Microarray

Pediatric B-cell acute lymphoblastic leukemia (B-ALL) is the most common childhood malignancy, and although event free survival has approached 90%, variability in disease outcomes still persists. At time of diagnosis, cytogenetic analysis of the leukemic clone currently dictates disease risk stratification, optimal therapeutic selection and overall prognosis. Cytogenetic analysis via conventional G-banded chromosome studies and fluorescence in situ hybridization (FISH) for the detection of recurrent rearrangements and characteristic gains and losses is the current gold standard. With the implementation of single nucleotide polymorphism (SNP)-based microarray tools within clinical laboratories (CytoScanHD and OncoScan/Affymetrix), a more precise characterization of B-ALL clones can be achieved. Here we demonstrate the utility of a SNP microarray in 4 illustrative pediatric patient cases seen at the Mayo Clinic Cytogenetics Laboratory to appropriately classify a variety of clinically significant B-ALL clones, including distinguishing hyperdiploidy versus pseudo-hyperdiploidy resulting from a doubled hypodiploid clone, identifying partial homozygous microdeletions of clinically-significant genes (e.g. CDNK2A/B and IKZF1) that fall below the resolution of FISH, and clarifying intrachromosomal amplification of chromosome 21 (iAMP21) unresolved by chromosome and FISH evaluation. These data indicate that the integration of a SNP-based microarray, along with concurrent chromosome and FISH evaluations, offers the most comprehensive cytogenetic analysis of a B-ALL clone.

2 - Development of a Clinical Grade Interpretive Tool for Neoplastic Genomic Microarray Testing

The identification of chromosomal abnormalities in solid tumor and hematologic malignancies is important for disease diagnosis, prognosis, progression, and therapeutic decision making. The recent application of a range of powerful molecular technologies including chromosomal microarray and next generation sequencing has dramatically increased the resolution of clinical genomic testing, leading to increased precision in the evaluation of the cancer genome. In the era of complex tumor genomics, a comprehensive and clinically-vetted knowledge base is critical to providing efficient, accurate and informative clinical interpretations. Although several public databases/resources are available, comprehensive clinical-grade resources directly facilitating interpretation and reporting of neoplastic microarray cases are still lacking. To achieve this goal, the Mayo Clinic Cytogenetics Laboratory is manually assembling and curating a comprehensive knowledge base of specific genes and genomic regions of clinical relevance, including a pan-cancer gene list and disease-specific gene lists for major groups of solid tumors and hematologic malignancies. Here we describe our processes, data sources, and annotation conventions. We also describe how we utilize Affymetrix Extensible Data (AED) files to visualize our curated gene lists alongside microarray findings, which facilitates scrutiny of relevant critical regions and rapid recognition of clinical significance. Using these newly created cancer interpretive tools we have built thus far, we have successfully provided efficient, accurate and informative interpretation of neoplastic microarray cases. We hope to share our experience with the CGC group and encourage community sharing of resources to facilitate best practices in neoplastic genomic microarray testing.

Cytogenetics at the University of Cape Town: A 45-year journey

This article is a brief record of the cytogenetics laboratory from its birth in 1971, under the auspices of the University of Cape Town, throughout its development within the Department of Human Genetics, under the leadership of Professor Peter Beighton, to its present position at Groote Schuur Hospital, as a multidisciplinary unit run by the National Health Laboratory Service.

Delay and poor diagnosis of Down syndrome in KwaZulu-Natal, South Africa: A retrospective review of postnatal cytogenetic testing.

Down syndrome (DS) is the most common chromosomal disorder in newborns. Until 20 years ago DS was considered rare in black African children in South Africa (SA). Lack of awareness of DS on the part of medical staff in SA, and difficulty in diagnosing it, appear to persist. To establish an epidemiological profile of DS and investigate the ability of clinicians in KwaZulu-Natal Province (KZN), SA, to make accurate clinical diagnoses of DS. Records at the South African National Blood Service cytogenetic laboratory in Pinetown, KZN, were examined for all tests for clinically suspected DS undertaken during January 2009 - December 2013 and all cytogenetically proven DS test results. Age at diagnosis, the hospital from where the test was sent and type of chromosomal pattern for each confirmed DS test result were recorded. Of a total of 1 578 tests requested, 875 confirmed DS, indicating that clinicians correctly clinically diagnosed DS 55.4% of the time. The average age of cytogenetic diagnosis of DS was 1 year and 20 days.The minimum population prevalence of DS was 0.8/1 000. The diagnosis of DS is a challenge in KZN, potentiating missed opportunities for early intervention. The relatively low population prevalence of DS may be attributable to a lack of confirmatory cytogenetic tests or missed clinical diagnoses. It may also be attributable to a high mortality rate for children with DS in the province.

21 - Characterization of Chromosome Translocation Breakpoints in Leukemia Using Whole Genome Mate-Pair Sequencing

Translocations are common in hematological neoplasms, some of which are known to play critical roles in disease pathogenesis. However, the clinical significance of the remaining translocations, particularly the uncommon ones, remains unknown due to lack of effective characterization methods. We developed a simple and straightforward strategy, employing mate-pair sequencing, free online data analysis tools and Microsoft Excel, to characterize breakpoints of translocations. Using this strategy, we characterized three translocations detected by chromosome analysis in patients with leukemia. The results demonstrated a fusion between KAT6A intron 16 and CREBBP intron 1 (leading to a type I KAT6A/CREBBP gene fusion) in a recurrent t(8;16)(p11.2;p13.3) translocation, and two different enhancer-MECOM gene fusions in two cytogenetically indistinguishable t(2;3)(p23;q26.2) translocations. These findings revealed possible contributions of the translocations to the disease pathogenesis and also showed that this strategy is efficient and effective, and it can be easily adopted in cytogenetics laboratories.

5 - Clinical Impact of Genomic Duplications: A Discussion of Reporting Practices

The Mayo Clinic Cytogenetics Laboratory has performed microarray-based detection of copy number variation (CNVs) since 2006. Currently, postnatal CNV reporting criteria include deletions greater than 200 kb and duplications greater than 500 kb, as well as any known pathogenic CNV regardless of size. These thresholds are in place in an attempt to maximize diagnostic findings while minimizing the return of uncertain variants. However, our experience with small duplications (less than 2 Mb) reveals that the vast majority are inherited, challenging the clinical utility of reporting such variants. We performed a retrospective review of >4000 reported duplications in an effort to refine our reporting criteria for duplications. Our results suggest limited diagnostic utility for reporting duplications less than 1Mb that do not involve known triplosensitive genes.

62 - Clinical Validation of a Simple FISH Assay That Uses 1 µl of Probe

Fluorescent in situ hybridization (FISH) using DNA probes is used by all cytogenetics laboratories for detecting chromosomal aberrations in human cancers. However, the high cost of DNA probes and a labor intensive workflow, coupled with the recent dramatic reductions in reimbursements, threaten the economic viability of FISH-based tests.

39 - Pre-Phase Chemotherapy for Acute Lymphoblastic Leukemia: A Cautionary Tale

A 58-year old female presented to UNC Hospitals with generalized pain, weakness and profound thrombocytopenia. Peripheral smear review revealed blasts raising concern for acute leukemia. An aspirate could not be obtained during bone marrow biopsy, and therefore peripheral blood was submitted for flow cytometry and molecular studies (PCR for BCR/ABL1). Flow findings were most suggestive of B cell acute lymphoblastic leukemia (B-ALL), which combined with progressive thrombocytopenia prompted initiation of a pre-phase chemotherapy regimen: cyclophosphamide, oncovin/vincristine, and prednisone (COP/CVP). Blood was drawn on day 3 of the pre-phase regimen and sent to the cytogenetics laboratory as a “diagnostic sample\” for karyotype and BCR/ABL1 FISH studies. Two days after this sample was received, a normal BCR/ABL1 FISH result was conveyed verbally to the physicians. An hour later, the technologist reading the G-banded slides found one metaphase with an apparent der(9)t(9;22) in the otherwise normal preparation. The technologist called the molecular laboratory and found that they had identified mutant BCR-ABL1 p190 transcripts (29,267 transcripts in 100,000 cells) from the blood sample drawn prior to pre-phase treatment initiation, though this result was not yet released. This positive result was quickly conveyed to the clinicians. The clinicians were deciding between treatment with hyperCVAD (cyclophosphamide, vincristine, adriamycin, dexamethasone) (BCR/ABL1 negative disease) and dasatinib/prednisone treatment (BCR/ABL1 positive disease), and were able to immediately proceed with the dasatinib treatment.

36 - Development of a Chromosomal Microarray Test for the Detection of Abnormalities in Formalin-Fixed Paraffin-Embedded Products of Conception Specimens

Testing the products of conception (POCs) provides information about the cause of fetal loss and helps determine the recurrence risk of future losses and chromosome abnormalities in subsequent pregnancies. Historically, the Mayo Clinic Cytogenetics Laboratory performed targeted fluorescent in situ hybridization (FISH) testing to identify aneuploidy of only certain chromosomes in formalin-fixed, paraffin-embedded (FFPE) POC samples. Chromosomal microarray studies using the Affymetrix OncoScan FFPE Assay can detect copy number changes across the genome. We validated the utility of the OncoScan assay using 25 archival FFPE POC specimens with previous FISH results (five normal, 12 trisomy, six triploidy, two monosomy). Of the five normal samples, four had no clinically relevant findings, and one sample was found to have trisomy 9, which is not detectable by the FISH test. For the 20 samples with abnormal FISH results, the OncoScan assay identified all reported abnormalities along with additional findings. A sample with trisomy 22 was also found to have trisomy 7. Another sample reported as triploidy was found to have four copies of chromosome 16. In conclusion, we verified the performance characteristics of OncoScan on FFPE POC specimens and found it acceptable for clinical use. Additional information was identified in 3 of 25 cases (12%) that would explain the pregnancy loss or provide recurrence risk for the family.

16 - Next Generation Cytogenetics: Genome-wide Mate Pair Sequencing for Detection of Structural Rearrangements and Copy Number Variation

While next generation sequencing has been rapidly adopted in clinical laboratories for detection of sequence level variants, and to some degree, copy number variation, the detection of structural variation through traditional paired end sequencing approaches is inherently problematic. Mate-pair sequencing, utilizing a modified library preparation capable of paired end sequencing from much longer fragments, is a powerful new strategy used to detect and characterize balanced structural rearrangements throughout the genome, without the need for targeting. The Mayo Clinic Cytogenetics Laboratory has been working to develop a clinical mate-pair sequencing strategy for genome-wide structural variation and copy number detection. This assay and a novel associated bioinformatics pipeline has been developed in partnership with the Mayo Clinic Center for Individualized Medicine. Our initial familiarization experiments demonstrate that this assay is robust with remarkable sensitivity and specificity for structural and copy number variation in constitutional and neoplastic samples. We will discuss the promise of this technology, the associated limitations, as well as our planned approach to clinical validation of an assay of this complexity. We will also discuss the critical need for clinical-grade interpretive aids, particularly for tumor analysis, as the number of detected events often exceed a scale that is manageable with current manually-driven interpretive approaches.

Survey of medical genetic services in Italy: year 2011.

BackgroundThe aim of this study was to collect information about 2011 genetic activities in Italy, with the purpose of providing guidance to the national health systems in order to improve genetic services.MethodsA web-based survey was carried out to achieve the information.ResultsData were collected from 268 macrostructures hosting 517 services and employing 3246 persons. About 295,000 cytogenetic, 35,000 immunogenetic and 263,000 molecular genetic analyses of 902 genes were recorded. Seventy-four percent of the services were accredited with institutional bodies and 57 % were also certified according to ISO 9001 standard. Twenty percent of cytogenetic laboratories had participated in an European External Quality Assessment (EQA) while 44 % participated in a national EQA. Only 28 % of the molecular laboratories had participated in a national Cystic Fibrosis EQA. The percentage of diagnoses confirmed by genetic tests varied among disorders, ranging from 52 % for coeliac disease to 4 % for fragile X syndrome.ConclusionsThis study highlights the need for reorganizing the Italian genetic services network, improving EQA participation and developing national plans for implementing next generation technologies. Concerted effort has to be addressed in the education of the professionals prescribing tests to improve appropriateness and to inform patients, who now have exposure to direct-to-consumer multifactorial genetic testing where clinical utility is unproven.

A novel Xq22.1 deletion in a male with multiple congenital abnormalities and respiratory failure

Here we report the first male case of a novel Xq22.1 deletion. An 8-week-old boy with multiple congenital abnormalities and respiratory failure was referred to the Mayo Clinic Cytogenetics laboratory for testing. Chromosomal microarray analysis identified a novel 1.1 Mb deletion at Xq22.1. A similar deletion has only been described once in the literature in a female patient and her mother; both have intellectual disability and dysmorphic facial features. In addition, the mother had a son who died at 15 days due to breathing failure. Recently, a mouse model revealed that a 0.35 Mb sub-region, containing 4 genes, is sufficient to cause majority of the Xq22.1 deletion phenotypes. The deleted intervals in our male patient and the female patients contain 15 common genes, including the four described in the 0.35 Mb sub-region. Male mice with deletion of the 0.35 Mb sub-region died perinatally from respiratory failure due to pulmonary hypoplasia, consistent with the breathing problem and potential neonatal fatality in male patients. The phenotypes of the mouse models and the patients are strikingly similar; therefore, the deletion of these five genes (ARMCX5, ARMCX5-GPRASP2, GPRASP1, GPRASP2, and BHLHB9) is likely responsible for the novel Xq22.1 deletion syndrome.

Probing the Complexities of Myelodysplastic Syndromes

![Graphic][1] Marilyn L. Slovak, PhD, FACMG, MT(ASCP), began her distinguished career as a medical technologist. After earning her PhD in regulatory biology, she went on to serve as cytogenetic laboratory director at the City of Hope Comprehensive Cancer Center in Duarte, Calif., for over 20 years before becoming medical director of Cytogenetics at Sonora Quest Laboratory in Tempe, Ariz., in 2012. She retired July 2015 and now does consulting. Dr. Slovak served on the International Cytogenetics Committee for Myelodysplastic Syndromes (MDSs) and in collaboration with Dr. Peter Greenberg and the International Working Group for Prognosis in MDS (IWG-PM) revised the International Prognostic Scoring System, or IPSS (1997), for MDS. The IPSS-R (revised) is regarded as the international gold standard classification system for MDS. This scoring system estimates overall survival and risk of transformation to acute myeloid leukemia (AML) in patients with primary MDS. The IPSS-R introduces several novel components, including five rather than three cytogenetic prognostic subgroups of IPSS (1997) with specific and new classifications of a number of less common cytogenetic subsets, splitting the low marrow blast percentage value, and depth (instead of the number) of cytopenias. Dr. Slovak also served on the faculty that developed the curriculum for the four MDS Summit workshops funded by an education grant from Celgene, that ASCP has co-hosted with the American Society of Hematology (ASH). She took time recently for an interview with ASCP about her involvement in both endeavors. Critical Values: Tell us about the MDS workshops and how this education translates into better patient care. Marilyn Slovak : Because MDS is a heterogeneous disease of myeloid clonal hemopathies, many hematologists/on-cologists have found great value in the IPSS-R system for estimating the overall survival and risk of transformation to AML in a patient with a new diagnosis of MDS. A time-sensitive complicating … [1]: /embed/inline-graphic-1.gif